The aim of this program is to analyze basic developmental mechanisms in higher animals. We wish to understand the as yet unknown processes which control spatial patterns of differentiation, also the processes which initiate and maintain determination, the heritable commitments made by cells which are transmitted to their mitotic progeny. We employ Drosophila as our experimental system because it is ideal for genetic manipulations and permits an enormous variety of experiments which are not possible with other animals. One goal is to identify the factors in the egg cytoplasm which appear to control nuclear activity and to direct early embryonic development. We have shown that some of these factors (germ cell determinants) can function after transfer to a host egg, and we propose to begin biochemical studies to identify the active materials. We are also analyzing maternal effect mutations which alter the organization of the egg in order to discover to what degree the egg cytoplasm laid down by the mother plays a causative role in determination. A second goal is to identify factors in somatic cells which are responsible for the maintenance of the determined state. We have devised a new method of producing cytoplasmic chimeras between eggs and somatic cells which may permit us to identify these factors. A third goal is to understand the mechanisms of pattern formation and intercellular communication. To this end we are analyzing imaginal discs by means of microsurgical and genetic techniques. Two important new approaches are a procedure for grafting imaginal discs and a novel way of locally manipulating patterns of cell death by means of autonomous temperature-sensitive cell lethal mutations. To test the applicability of our findings to vertebrates, we have extended our studies of pattern formation to the regenerating amphibian limb.